The in vivo antiangiogenic activity and in vitro cytotoxic effects of methanol leaf extract of Leonotis leonurus (Lamiaceae) against A2780 human ovarian cancer cells are investigated in this work. Leonotis leonurus (L. leonurus), a fellow of the Lamiaceae family and commonly Referred to as "wild dagga," or “lion’s ear” is a commercially important plant The antiangiogenic capacity was evaluated with the Avian chorioallantoic membrane (CAM) assay to reveal 100% inhibition of blood vessel growth at 500 mg/mL. Cytotoxicity was measured using the MTT assay; a dose-dependent drop in cell viability resulted from an IC50 value of 93.22 µg/mL. Phytochemical analysis investigation detects the presence of significant amounts of phenolic acids (chlorogenic acid: 342.7 ppm; caffeic acid: 106.11 ppm) and flavonoids (resveratrol: 665.4 ppm; apigenin: 280.2 ppm) using reversed-phase HPLC with novel isolation of resveratrol from the plant for the first time. The presence of these phytochemical is linked to angiogenesis suppression and death induction. Statistical analysis (Tuk's test) with p < 0.05 confirmed notable cytotoxic effects at all dosages. These findings highlight L. leonurus as a possible natural source of bioactive compounds with cytotoxic and antiangiogenic properties, hence worthy of future investigation for the creation of anticancer treatments.